Turkish Journal of Pathology - 2019; 35(2)

BRAFV600E Immunohistochemistry in Papillary Thyroid Carcinomas: Relationship Between Clinical and Morphological Parameters

Faruk Erdem KOMBAK, Naziye �ZKAN, Mustafa �mit U�URLU, Handan KAYA — 2019-05-01

Objective: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR). Material and Method: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly. Results: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered �positive�. The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension. Conclusion: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in the Diagnosis of Hilar and Mediastinal Lymph Node Metastases of Melanoma

2019-05-01

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for investigating hilar and mediastinal lymphadenopathy. This study reports eleven cases in which EBUS-TBNA was used to assess mediastinal and hilar lymph nodes for the presence of metastatic melanoma. Material and Method: A retrospective study was performed of all patients who had a history of melanoma and underwent EBUS-TBNA to assess hilar or mediastinal lymphadenopathy for the presence of metastatic melanoma. In seven cases, molecular analysis to detect mutations in the BRAF gene was also used. Results: Eight patients had been diagnosed with malignant melanoma in the past (mean 54.4 months, range 18 to 115 months) while in the other three this tumor was primarily diagnosed in the staging phase. The male-female ratio was 6:5, and the mean age was 60.3 years (range 42 to 88 years). The mean hilar or mediastinal lymph node size detected with computed tomography was 3.0 cm (range 1.1 to 8.1 cm). Eight (72.7%) cases had metastases to the lung associated with metastases in the mediastinal lymph nodes. In four (50%) of these cases, the lung metastasis was solitary. Three (27.3%) cases had metastases in the mediastinal lymph nodes in absence of lung metastases. Metastatic melanoma was diagnosed by cytology and confirmed by cell block study with immunohistochemistry in all cases. BRAF mutations were detected in two (28.6%) of seven cases studied. Conclusion: Cytology and tissue samples obtained from EBUS-TBNA are adequate to detect metastatic melanoma and permit in some cases the determination of biomarkers and identify the presence or absence of mutations in the BRAF gene. The procedure is safe, fast, and precise for the staging of melanoma.

Two-Year Results of Community-Based Screening Program for Human Papilloma Virus DNA in �orum Province

G�ven G�NEY, Emine ARSLAN, Y�lmaz BA�, Ebru TURGAL — 2019-05-01

Objective: The Turkish Ministry of Health started a community-based screening program using Human Papilloma Virus (HPV) DNA in 2014. In our study, we aimed to investigate the results of this survey in �orum province between the years of 2016-17 to determine the shortcomings and deficiencies in practice. Material and Method: All of the women between the ages of 30 and 65 years who had undergone High risk HPV DNA screening in �orum province between 2016 and 2017 were included in the study. High risk HPV types were divided into three categories as type 16, 18 and others. The target group of patients to be screened were compared with the numbers reached in the survey. After colposcopic biopsy, the clinicopathological correlation of the patients who underwent colposcopic biopsy was determined via pathology reports. Results: HPV DNA was detected in 817 women (3.5%). HPV types 16, 18 and others were found to be positive in 216, 32 and 569 individuals, respectively. Cervical biopsy was performed with colposcopy in 212 (26%) women. As the result of colposcopy, LSIL and HSIL were detected in 63 and 56 patients, respectively. 34.5% of patients with the diagnosis of any kind of dysplasia received treatments. Conclusion: It was determined that 44% of HPV DNA-positive patients were not subjected to the appropriate processes according to the national guidelines. This shows that despite the screening, the desired therapeutic effect could not be achieved.

Histopathological Changes of Placenta in Meconium Stained Liquor and Its Relevance in Fetal Distress: A Case Control Study

Tanima ROY MONDAL, Goutam BANDYOPADHYAY, Sabuj Ghana MUKHOPADHYAY, Dyuti GANGULY — 2019-05-01

Objective: Meconium passage during labour is a quite common finding. Studies describing correlation between meconium stained liquor, fetal distress and specific placental pathology are sparse. This case control study had been designed to ascertain these lacunae of knowledge. Material and Method: Placentae from 41 cases of otherwise uncomplicated antenatal and intranatal pregnancies with meconium stained liquor at 37 completed weeks of gestation were studied, both grossly and microscopically, comparing them with controls of 41 cases of clear liquor. Apgar score of all newborns at 1 minute and 5 minutes were recorded and correlated with histopathological findings. Results: Both cases and controls were found to be age matched. Meconium stained liquor was associated with more caesarian section than the clear ones. Significant correlation was found with meconium stained liquor and low Apgar scores. Histopathology of placenta revealed many statistically significant associations between specific placental histopathology in meconium stained liquor and depressed Apgar score. Evidence of placental vasculopathy rather than meconium induced placental damage came out as the potential culprit in causing a low Apgar score in this case control study. Conclusion: Placental vascular changes have a role in meconium staining of liquor. If timely interventions are taken, the chance of development of fetal distress is low.

The Relationship Between Obesity, Insulin Resistance, and Conjunctival Impression Cytology

2019-05-01

Objective: This study was designed to determine whether obesity causes the development of metaplasia in conjunctival epithelial cells. Material and Method: A total of 61 volunteer participants who had no previous history of illness or drug use were involved in this study. Of those, 20 were obese, and 41 were of normal weight. We measured the glucose and insulin values of all volunteers. We also measured the Body Mass Index (BMI) and Homeostasis Model Assessment for Insulin Resistance (HOMA IR). The impression cytology method was used to analyze the conjunctival epithelium cells, and to classify them between Grades 0 to 3 according to the Nelson criteria. Results: There was a certain level of loss of goblet cells on the 90% level as well as squamous metaplasia (Grade 2-3) in 80% of the obese participants and impression cytology was found to be normal in only two patients. The expected results were observed in 56.1% of the control group where the squamous metaplasia rate was nearly 17% (p<0.001). 90.9% of the grade 3 patients were obese. The variables as independent predictors were found to indicate the existence of abnormal cytology in the conjunctiva at various levels; BMI (OR: 1.24; p=0.002) and HOMA IR (OR= 28.6; p= 0.001) in a Model I multivariable regression model, and the existence of obesity (OR: 11.91; p=0.002) and HOMA IR (OR= 15.08; p<0.001) in a Model II multivariable regression model. Conclusion: Obesity was found to be a disorder that causes metaplasia in the conjunctival epithelium cells for the first time.

Are all Granulomatous Mastitis Cases Tuberculous?: A Study on the Role of Cytology in Evaluation of Granulomatous Mastitis

2019-05-01

Objective: Granulomatous mastitis is a rare inflammatory condition of the breast clinically mimicking breast carcinoma and pyogenic abscess, thereby creating a diagnostic dilemma. Tuberculous mastitis is a rare clinical entity accounting for approximately 3% of all mammary lesions. All cases of granulomatous mastitis diagnosed cytologically over a period of 3 years were evaluated to ascertain the cases with tuberculous etiology. Material and Method: Fine needle aspiration cytology of the breast lump was performed and all the cytological parameters were evaluated. Wherever histopathology was available, the diagnosis was confirmed on Hematoxylin & Eosin stained sections and the Ziehl Neelsen (ZN) stain was applied. Results: A total of 10 cases of granulomatous mastitis were diagnosed on cytology during the 3-year period. On cytological smears, four cases showed presence of ill-formed granulomas and one case had scattered epithelioid histiocytes; however, the rest of the cases had well-formed granulomas. Finally, four out of ten cases were labeled as tuberculous mastitis based on the ZN stain/Tuberculosis-Polymerase chain reaction (TB-PCR) and the other six cases were granulomatous mastitis. Conclusion: Cytology plays a significant role in the diagnosis of granulomatous mastitis. This study re-emphasizes the role of the cytopathologist in the accurate and early diagnosis of these lesions so that unnecessary surgery can be avoided, and also highlights the fact that all granulomatous mastitis cases are not tuberculous.

Usefulness of WhatsApp for Discussing Difficult Cases in Pathology Practice: A Moroccan Experience

Amal BENNANI, Mohammed SEKAL — 2019-05-01

Objective: The primary aim of the study was to evaluate whether the WhatsApp application can be used for obtaining a quick second opinion on histopathological and cytological diagnosis and also for discussing difficult cases in pathology practice. Material and Method: A WhatsApp group named �FESPATH� was created with total of 17 pathologists (the authors of this manuscript as group administrators and 15 general pathologists from 7 different cities in Morocco, working in 12 different institutions as members). The group was used to discuss difficult routine sign out cases, to obtain a second opinion. Pathology-related academic files, books and links were also shared. At the end of 20 months, members were asked to complete a feedback questionnaire. Results: Over a 20-month period, 86 cases were discussed with 515 posted pictures. 78 cases were related to histopathology, and 8 cases to cytopathology. Twenty-one links regarding educational materials and books were also shared. A total of 14 participants out of 17 were active participants, and the majority of them found the discussions very useful for overcoming challenging cases. Conclusion: Sharing microphotographs of histopathological or cytological cases via WhatsApp is a very easy and fast method to obtain a second opinion in pathology practice and also to discuss difficult cases.

Therapy-Induced Neural Differentiation in Ewing's Sarcoma: A Case Report and Review of the Literature

2019-05-01

Ewing's sarcoma (ES) is a small round cell tumor of adolescents or young adults that usually arises in the deep soft tissues of the extremities. The tumor cells have uniform round nuclei, fine powdery chromatin and indistinct nucleoli. CD99 (O13) is a product of the MIC 2 gene that is highly sensitive to ES but not specific. A panel of markers should be used for the differential diagnosis of small round cell tumors because nearly all others, on occasion, show membranous staining for CD99. One of the defining feature of ES is the presence of 22q12 gene rearrangement. The presented case is a 6 year-old boy complaining of swelling on his right leg. The biopsy was compatible with classic ES in terms of histopathological, immunohistochemical and cytogenetic criteria. Wide surgical resection was performed after chemotherapy. The posttreatment specimen was composed of uniformly small round cells mixed with areas of ganglion cells embedded in neurophil-like fibrillary background. Immunohistochemically, neoplastic cells revealed strong CD99 (O13) and NSE staining and the tumor had EWSR1 gene rearrangement. Morphologic alterations due to treatment are commonly seen in pediatric tumors. Single case reports have defined neural differentiation in ES but to the best of our knowledge this is the first report of ES in the literature with all histopathological, immunohistochemical, and cytogenetic criteria evaluated in both pretreatment and posttreatment specimens.

Xanthogranulomatous Pancreatitis -A Rare Case Defying Clinical, Radiological and Tumor Marker Diagnostics with a Review of Literature

Kavita GAUR, Shramana MANDAL, Nidhi MAHAJAN, Sandeep SALUJA, Satyajit GODHI — 2019-05-01

Xanthogranulomatous inflammation of the pancreas is an extremely rare entity mimicking pancreatic neoplasia. Elevation of tumor markers has seldom been reported in xanthogranulomatous inflammation of the pancreas, rendering the diagnosis difficult and highlighting the importance of a meticulous histopathological examination. A 58-year-old male presented with severe abdominal pain and anorexia for six months. A heterogeneously enhancing solid cystic mass was detected in the pancreatic head on contrast enhanced computed tomography. Endoscopic ultrasound guided aspiration yielded fluid showing elevated levels of CA19-9 (12000 IU/ml) and CEA (221ng/ml) with a concordant increase in the serum tumour marker levels (CA 19-9:407 IU/ml; CEA: 70 ng /ml). Clinical, radiological and biochemical evidence favouring malignancy prompted a Whipple's procedure. A thorough histopathological examination of the specimen failed to reveal malignancy. Sheets of macrophages (CD 68 +, HAM 56 +), chronic inflammatory cells, fibroblasts and proliferating capillaries replacing most of the pancreatic parenchyma were seen instead, nailing the diagnosis of xanthogranulomatous inflammation of the pancreas. To the best of our knowledge this is the first report of xanthogranulomatous inflammation of the pancreas without associated malignancy displaying an elevation of serum and fluid tumour markers. After seven months of follow up, the patient is asymptomatic and is doing well.

Inflammatory Myofibroblastic Tumor of the Stomach Presenting as an Exophytic Mass - A Diagnostic Dilemma

Meena JADHAV, Rekha HARVI, Rashmi PATIL, Shreekant KITTUR — 2019-05-01

Inflammatory myofibroblastic tumor is an uncommon soft tissue neoplasm of uncertain biologic behavior, and rarely reported in the stomach. An eighteen-year-old male presented with a mass in the epigastrium of three-month duration. Clinical and radiological examination suggested a gastrointestinal stromal tumor or a leiomyoma in the lesser curvature of the stomach. On the basis of histomorphological features and immunohistochemical analysis the diagnosis of inflammatory myofibroblastic tumor in the lesser curvature of the stomach was made. Inflammatory myofibroblastic tumor should be considered in the differential diagnosis of soft tissue tumors of the stomach.

Water-Clear Cell Adenoma of the Mediastinal Parathyroid Gland

Deniz ARIK, Emine D�NDAR, Evrim YILMAZ, Cumhur S�VR�KOZ — 2019-05-01

Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.

Ambiguous Genitalia Associated with an Extremely Rare Syndrome: A Case Report of XLAG Syndrome and Review of the Literature

Brijnandan GUPTA, Prashant RAMTEKE, V K PAUL, Tarun KUMAR, Prasenjit DAS — 2019-05-01

X-linked lissencephaly, absent corpus callosum, and epilepsy of neonatal onset with ambiguous genitalia comprises the XLAG syndrome and only 15 cases have been reported in literature. Due to its rarity, the exact clinical course and outcome are not known. Exact associations of this disease are also elusive. Hereby we are reporting this extremely rare entity and we searched the English literature extensively to get consolidated knowledge regarding this entity that would help the readers. Pre-natal radiological work-up can detect these malformations, which should be followed by medical termination, counseling and karyotyping. Till date the longest survival noted was 4 years only.

Pulmonary Hydatid Disease with Aspergillosis - An Unusual Association in an Immunocompetent Host

Rahul Chanderhas GOYAL, Ruchita TYAGI, Bhavna GARG, Atul MISHRA, Neena SOOD — 2019-05-01

Echinococcosis is a common cause of pulmonary cavities. Aspergillus fumigatus, a saprophytic fungus, can colonise pulmonary cavities caused by tuberculosis, sarcoidosis, echinococcosis, bronchiectasis and neoplasms. Infection by Aspergillus is often seen in immunosuppressed cases. However, co-infection of Aspergillus with pulmonary echinococcosis is unexpected and very unusual, especially in an immunocompetent patient. We present the case of a 45-year-old immunocompetent male who came with non-resolving pneumonia and fever for 8 months and dyspnoea since 15 days accompanied by recurrent episodes of hemoptysis since 5 days. Chest X Ray and Computed Tomography scan showed a cystic lesion in the middle lobe of the right lung. Middle lobectomy with video-assisted thoracoscopic surgery was performed and histopathology revealed ectocyst of Hydatid cyst which was also colonised by septate fungal hyphae exhibiting acute angled branching, morphologically consistent with Aspergillus. Gomori Methanamine Silver and Periodic Acid Schiff stains highlighted the hyphae of Aspergillus as well as the lamellated membranes of ectocyst and an occasional scolex of Echinococcus. Sections from surrounding lung parenchyma also showed these fungal hyphae within an occasional dilated bronchus. Thus a diagnosis of dual infection of Aspergillosis and Pulmonary Echinococcosis was established. The possibility of dual infection by a saprophytic fungus must be kept in mind while dealing with a case of a cavitary lesion in long-standing and non-resolving pneumonia, even in an immunocompetent patient. Establishing the correct diagnosis of Aspergillosis with Echinococcosis is essential for proper and complete management.

Poster Colours: Pocket-Friendly Alternative to Tissue Marking Dyes

Mardiana ABDUL AZ�Z, Nor Salmah BAKAR, Noor Kaslina MOHD KORNAIN — 2019-05-01